Abstract:

To fight pathogens is a major challenge of the immune system and it involves a cascade of mechanisms coupled together to defend the body against harmful stimuli. Injection of the endotoxin Lipopolysaccharide (LPS), a part of the cell wall of gram-negative bacteria activates peripheral immune cells and provokes an inflammatory cytokine response propagating to the brain. Aim of this work is to investigate the in vivo functional properties of cortical networks during peripheral inflammation. Our results demonstrate that under inflammatory conditions, the properties of the cortical network in the intact brain are shifted towards a hyperactive state. Microglia and neurons react to peripheral inflammation, induced by LPS injections, with a clear increase of their spontaneous calcium signaling. By using in vivo two-photon-calcium-imaging, we characterized the behavior of these two cell types over time and provided insights into the mechanisms involved. We found evidence that the activation of specific cytokines is underlying the altered brain signaling and showed that neurons react to this inflammatory condition in a microglia-independent manner.